ffr versus ivus with angiography-derived ffr for clinical outcomes in patients with coronary artery disease

Conditions: Coronary Artery Disease

Summary: to compare the clinical outcomes of fractional flow reserve (ffr)-guided strategy versus intravascular ultrasound (ivus)-guided stent implantation after angiography-derived ffr-based decision-making.

1. hypothesis: the ivus-guided stent implantation after angiography-derived ffr-based decision-making will show superiority in terms of a lower rate of patients-oriented composite outcomes (poco) at 24 months after randomization compared with the ffr-guided pci strategy in patients with coronary stenosis. 2. research materials and indication for revascularization: 2.1 experimental group: pci will be performed if angiography-derived ffr ≤0.80 and will be deferred if angiography-derived ffr \>0.80; if pci is performed, pci optimization using ivus will be performed following the recommended criteria: ① plaque burden at stent edge ≤55%; ② minimal stent area ≥ 5.5 mm2, or minimal stent area ≥ distal reference lumen area. 2.2 control group: pci will be performed if ffr ≤0.80 and will be deferred if ffr \>0.80; if pci is performed, pci optimization using ffr will be performed following the recommended criteria: ① post-pci ffr ≥ 0.88, or ② post-pci δffr (\[ffr at stent distal edge\] - \[ffr at stent proximal edge\]) \< 0.05. 3. sample size: in the post-hoc analysis of the flavour i study applying qfr analysis, the 2-year poco rate was 13.0% in the pci group with ffr ≤0.80 and undergoing ffr-based pci optimization and 7.1% in the pci group with qfr ≤0.80 and undergoing ivus-based pci optimization. meanwhile, the 2-year poco rate was 5.8% and 6.5% in the deferral of pci group with ffr \>0.80 and qfr \>0.80, respectively. assuming a pci rate of 70% in patients with coronary artery lesions with 50-90% stenosis that is the inclusion criteria for the current study, and considering event rates from historical studies evaluating ffr- and qfr-guided pci strategies, the cumulative incidence rate of poco at 24 months was estimated to be 13.0% in the control group (ffr group) and 9.0% in the experimental group (qfr-ivus group). * primary endpoint: poco, defined as a composite of death from any cause, mi, or any revascularization at 24 months after randomization. * design: superiority * sampling ratio: experimental group : control group = 1:1 * type i error (α): one-sided 2.5% * accrual time: 24 months * total time: 4 years (accrual 24 months + follow-up 24 months) * assumption: poco 13.0% vs. 9.0% in control or experimental group, respectively * statistical power (1- β): 90% * primary statistical method: kaplan-meier survival analysis with log-rank test * estimated attrition rate: total 10% * stratification in randomization: presence of diabetes mellitus based on the above assumption, we would need total 1,942 patients (971 patients in each group) with consideration of an attrition rate.

Eligibility criteria:
inclusion criteria: * subject must be ≥ 19 years. * subject is able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving invasive physiologic or imaging evaluation and pci with a drug-eluting stent (des) and he/she or his/her legally authorized representative provides written informed consent. * subjects suspected with ischemic heart disease. * subjects with coronary artery diameter stenosis 50-90% by angiography-based visual estimation eligible for stent implantation. * target vessel size ≥ 2.5mm in visual estimation. exclusion criteria: * known hypersensitivity or contraindication to any of the following medications: heparin, aspirin, clopidogrel, prasugrel, ticagrelor * active pathologic bleeding. * gastrointestinal or genitourinary major bleeding within the prior 3 months. * history of bleeding diathesis, known coagulopathy. * non-cardiac co-morbid conditions with life expectancy \< 2 years. * target lesion located in coronary arterial bypass graft. * left main coronary artery stenosis ≥ 50%. * chronic total occlusion in the study target vessel. * culprit lesion of st-elevation myocardial infarction (stemi). * not eligible for angiography-derived ffr (ostial rca ≥ 50% stenosis, severe tortuosity, severe overlap, poor image quality).

Keywords: angiography-derived fractional flow reserve intravascular ultrasound fractional flow reserve percutaneous coronary intervention